Health care delivery to the elderly is a major component of the present health system and will become even more significant in the future. However, knowledge of the determinants affecting drug responsiveness in this population is even less well defined than in younger individuals, and the role of the aging process(es) in affecting the various factors is largely unknown. The major goal of the proposed research is to define in man some of the age induced changes which lead to alterations in the pharmacokinetics of disposition and pharmacodynamics thus permitting more rational and safer drug use in the elderly. The relative importance and contribution of altered disposition and cerebral sensitivity, as assessed by quantitative changes in the electroencephalogram and psychometric tests, caused by aging with the widely used benzodiazepines will be investigated. Both the acute and chronic situations will be studied using diazepam and lorazepam as model compounds. The disposition of meperidine will also be investigated to delineate the factors controlling this drug's pharmacokinetics after various routes of administration. Additionally, the effects of aging on the involved processes will be examined along with any changes in central receptor responsiveness. Finally, the question of drug interactions in the elderly will be addressed by examining the influence of aging on the rate and extent of development of enzyme induction of drug metabolizing enzymes using propranolol and rifampicin as model compounds.